Structural Insights into Yeast DNA Polymerase δ by Small Angle X-ray Scattering

Rinku Jain, Michal Hammel, Robert E. Johnson, Louise Prakash, Satya Prakash, Aneel K. Aggarwal

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

DNA polymerase δ (Polδ) is a multisubunit polymerase that plays an indispensable role in replication from yeast to humans. Polδ from Saccharomyces cerevisiae is composed of three subunits: Pol3, Pol31, and Pol32. Despite the elucidation of the structures and models of the individual subunits (or portions, thereof), the nature of their assembly remains unclear. We present here a small-angle X-ray scattering analysis of a yeast Polδ complex (PolδT) composed of Pol3, Pol31, and Pol32N (amino acids 1-103 of Pol32). From the small angle X-ray scattering global parameters and reconstructed envelopes, we show that PolδT adopts an elongated conformation with a radius of gyration (Rg) of ∼ 52 Å and a maximal dimension of ∼ 190 Å. We also propose an orientation for the accessory Pol31-Pol32N subunits relative to the Pol3 catalytic core that best agrees with the experimental scattering profile. The analysis also points to significant conformational variability that may allow Polδ to better coordinate its action with other proteins at the replication fork.

Original languageEnglish (US)
Pages (from-to)377-382
Number of pages6
JournalJournal of Molecular Biology
Volume394
Issue number3
DOIs
StatePublished - Dec 4 2009

Keywords

  • DNA polymerase
  • DNA replication
  • cancer
  • mutagenesis

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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